Genetic selection strategies: computer modeling

There are four primary factors to consider in genetic selection strategies: 1) accuracy of selection, 2) selection intensity, 3) effective population size, and 4) mating system. Current theory indicates that optimum response to selection is achieved by maximizing the first three factors and using a mating systems that allows optimization of reproductive characteristics in dam lines and production characteristics in sire lines. However, with limited resources, compromises among the first three factors are needed. Simulations are useful for examining those compromises. Unrealistic simplifying assumptions are necessary for analytic theoretical results and thus do not address real world breeding problems. Using simulations, the relationship between selection accuracy, which is increased by use of family selection indices or Best Linear Unbiased Prediction (BLUP), and response to selection was examined. Results show that those procedures place a great restriction on effective population size, which offsets most of their advantage, i.e., there is too little emphasis on effective population size. A revision of the methodology and a reappraisal of the results of selection theory for optimization of genetic response is required. Another relationship that is of fundamental importance in breeding programs is that between selection intensity and effective population size. Analytical results for the additive case have been developed but have never been extended to heterotic traits. A gene level simulation program was developed to examine that relationship. Results show that the optimal selection strategy depends on the trait being selected. For additive traits and in the short term (20 generations), one should maximize selection intensity. For heterotic traits, an intermediate proportion (25% of each sex) gives optimal response. In all breeding strategies, primary attention must be given to the rate of inbreeding, which is increased by increasing either accuracy of selection or selection intensity. Inbreeding reduces response to selection in two ways. First, for both additive and nonadditive traits, inbreeding is a measure of the amount of random genetic drift that has occurred. Genetic drift causes loss of favorable alleles. Once lost, those alleles can never be recovered and thus genetic drift lowers the selection limit. Second, for heterotic traits, inbreeding results in a depression of the mean caused by directional dominance.     

Absorptivity contrast in transillumination imaging of tissue abnormalities

We calculate the time-resolved flux of photons transmitted across an optically turbid slab containing a partially absorbing inclusion. An analytical expression is obtained for the flux at a detector positioned opposite a point source (at a distance equal to the thickness of the slab) when the center of the inclusion lies on the line connecting those points. The calculation employs a discrete-time lattice random-walk model of photon transport. The resulting expression is used to assess the affects of time resolution on the detectability of the inclusion.     

Bronchoalveolar lavage. Quantitation of intraalveolar fluid?

A precise calculation of the amount of intraalveolar fluid is the basis of a quantitative analysis of intraalveolar compounds. Different approaches have been made to cover this important problem. Here, we report a comparative study with five markers: 99mTc-DTPA, 51Cr-EDTA, inulin, urea, and methylene blue in animal experiments as well as in human experiments. The marker substances were added to the lavage fluid, and the "dilution" of the markers, i.e., the alveolar fluid, was calculated. The results showed that in animals with healthy lungs the tracer methods are able to calculate amounts of intraalveolar fluid that are comparable to morphologic findings. In animals as well as in humans, methylene blue and inulin were shown to be useless in determining alveolar fluid volume compared with the tracer methods. In humans, the calculations with the urea method and with Tc-DTPA were in the same magnitude, but there was no individual correlation. We conclude that, at present, the methods to quantitate alveolar fluid volume lack precision and add nothing to a deeper understanding of alveolar biology.     

Dynamics of temperature dependent optical properties of tissue:dependence on thermally induced alteration

Thermal damage in heated bovine myocardial tissue is assessed from measured changes in total reflection and transmission of light. Mathematical expressions, based on random walk analysis of light propagation within tissue slabs, are used to relate the diffuse reflection and transmittance to the absorption coefficient, μ_a , and effective scattering coefficient, μ'_s for samples of myocardial tissue which were subjected to rapid step changes in temperature. Time-dependent changes in μ'_s indicate two processes, one with a fast and temperature-dependent rate the other with a slow and apparently temperature-independent rate. For final temperatures above 56.8°C and for the first 500 s after the temperature change, the optical parameters are well fit by exponential forms that exhibit temperature-dependent time constants as predicted by Arrhenius reaction rate theory of thermal damage. The scattering changes are associated with an apparent activation energy, ΔE, of 162 kJ/mole and a frequency constant, A, of 3×10²³ s^-1 . This method provides a means for estimating optical coefficients which are needed to assess laser tissue dosimetry     

Regulation of presynaptic NMDA responses by external and intracellular pH changes at developing neuromuscular synapses

NMDA receptors play important roles in synaptic plasticity and neuronal development. The functions of NMDA receptors are modulated by many endogenous substances, such as external pH (pHe), as well as second messenger systems. In the present study, the nerve-muscle cocultures of Xenopus embryos were used to investigate the effects of both external and intracellular pH (pHi) changes on the functional responses of presynaptic NMDA receptors. Spontaneous synaptic currents (SSCs) were recorded from innervated myocyte using whole-cell recordings. Local perfusion of NMDA at synaptic regions increased the SSC frequency via the activation of presynaptic NMDA receptors. A decrease in pHe from 7.6 to 6.6 reduced NMDA responses to 23% of the control, and an increase in pHe from 7.6 to 8.6 potentiated the NMDA responses in increasing SSC frequency. The effect of NMDA on intracellular Ca2+ concentration ([Ca2+]i) was also affected by pHe changes: external acidification inhibited and alkalinization potentiated [Ca2+]i increases induced by NMDA. Intracellular pH changes of single soma were measured by ratio fluorometric method using 2,7-bis (carboxyethyl)-5, 6-carboxyfluorescein (BCECF). Cytosolic acidification was used in which NaCl in Ringer's solution was replaced with weak organic acids. Acetate and propionate but not methylsulfate substitution caused intracellular acidification and potentiated NMDA responses in increasing SSC frequency, intracellular free Ca2+ concentration, and NMDA-induced currents. On the other hand, cytosolic alkalinization with NH4Cl did not significantly affect these NMDA responses. These results suggest that the functions of NMDA receptors are modulated by both pHe and pHi changes, which may occur in some physiological or pathological conditions.